Therefore, as a result of evaluating the effect of betulin on the production and expression of TNF-α, IL-6, and IL-1β, which are known as pro-inflammatory mediators and representative inflammatory cytokines of periodontitis in PG-LPS-stimulated HPDL cells, betulin downregulates the protein production of 11β-HSD1 and transcription factor C/EBP β together with inhibition of iNOS and COX-2 proteins produced by PG-LPS, and 11β-HSD1 with increased pro-inflammatory cytokines. Here, NOS2 is linked to periodontitis.